Additional experiments investigating the effect of TNF-α on chemokine expression need to be carried out in order to elucidate further the cellular mechanisms that occur after TNF-α

injection. As rgpTNF-α acted synergistically with rgpIFN-γ in our in vitro studies, it will be interesting to investigate the effect of a combination Erlotinib ic50 of these two cytokines on virulent M. tuberculosis infection in the guinea pig model. It is becoming clearer that immune response to M. tuberculosis is mediated by multi-functional T cells [49], and a vaccine superior to BCG is yet to be identified to combat tuberculosis. Efforts leading to enhancing the immunomodulatory properties of BCG vaccine with recombinant BCG vaccine strains expressing multiple functional cytokines [50] in a relevant animal model of pulmonary tuberculosis would certainly boost our knowledge of the mechanisms of anti-bacterial immunity. This study was supported in part by USPHS, NIH grant Venetoclax cell line R01-15495 and a subcontract awarded to D. N. M. from Colorado State University under the NIH contract HHSN 266200400091c. The authors are thankful to Dr. Robert Alaniz and Jane Miller for their valuable assistance with the flow cytometry experiments. The authors greatly appreciate

the help from Dr. Bradley Weeks for evaluating the histological changes in the tissues. None of the authors has any conflict of interest. “
“Inflammation causes increases in the level of matrix metalloproteinases (MMPs), which, in central nervous system (CNS), are associated with neuroinflammation and disruption of blood–brain barrier. Analysis of cerebrospinal fluid (CSF) is

pivotal for detecting diseases in CNS and, although a specific diagnosis may for not be achieved, this analysis is helpful to confirm the diagnosis or to rule out relevant differential diagnoses. This study examined the levels of MMP-2 and MMP-9 in the CSF of dogs using gelatin zymography to verify possible alterations in these enzymes during natural systemic infection with Leishmania chagasi. Latent and active forms of MMP-2 were detected in some dogs of both groups, with high levels in the control group. In contrast, latent and active forms of MMP-9 were detected only in some animals with leishmaniasis. These results clearly demonstrate that MMP-9 is elevated in CSF of dogs with visceral leishmaniasis (VL). Although these results are preliminary, they suggest that MMP-9 might play a role in disruption of blood–brain barrier and/or blood–CSF barrier. While the presence of MMPs in CSF is not a condition exclusive to VL, their presence and persistence in CSF supports the hypothesis of an inflammatory state within CNS of dogs with VL. Canine visceral leishmaniasis (VL) is a zoonotic disease with a worldwide distribution. In South America, the number of infected dogs has been estimated to be in the millions, especially in some areas of Venezuela and Brazil, and, in the Mediterranean basin countries of Europe, at least 2·5 million dogs (16·7%) are infected (1).